Fluoxetine exposure in adolescent and adult female mice decreases cocaine and sucrose preference later in life.

backgroundPreclinical evidence from male subjects indicates that exposure to psychotropic medications, during early development, results in long-lasting altered responses to reward-related stimuli. However, it is not known if exposure to the antidepressant fluoxetine, in female subjects specifically, changes sensitivity to natural and drug rewards, later in life.

aimsThe aim of this work was to investigate if exposure to fluoxetine mediates enduring changes in sensitivity to the rewarding properties of cocaine and sucrose, using female mice as a model system.

methodsWe exposed C57BL/6 female mice to fluoxetine (250 mg/L in their drinking water) for 15 consecutive days, either during adolescence (postnatal day 35-49) or adulthood (postnatal day 70-84). Twenty-one days later, mice were examined on their behavioral reactivity to cocaine (0, 2.5, 5, 7.5 mg/kg) using the conditioned place preference paradigm, or assessed on the two-bottle sucrose (1%) test.

resultsWe found that regardless of age of antidepressant exposure, female mice pre-exposed to fluoxetine displayed reliable conditioning to the cocaine-paired compartment. However, when compared to respective age-matched controls, antidepressant pre-exposure decreased the magnitude of conditioning at the 5 and 7.5 mg/kg cocaine doses. Furthermore, fluoxetine pre-exposure reduced sucrose preference without altering total liquid intake.

conclusionsThe data suggest that pre-exposure to fluoxetine, during adolescence or adulthood, results in a prolonged decrease in sensitivity to the rewarding properties of both natural and drug rewards in female C57BL/6 mice.